Assistant Professor of Neurosurgery and, by courtesy, of Orthopaedic Surgery at the Stanford University Medical Center

Bio

Bio

Dr. Anand Veeravagu is Assistant Professor of Neurosurgery and Assistant Professor of Orthopedic Surgery, by courtesy, and Director of Minimally Invasive NeuroSpine Surgery here at Stanford. Dr. Veeravagu is focused on advancing minimally invasive surgical techniques for diseases of the spine and cares for patients with a wide range of spinal disorders.

Dr. Veeravagu graduated from the Johns Hopkins University Biomedical Engineering program with a focus on spinal cord injury and regeneration. Committed to medical device development, neuroregeneration, and non-invasive imaging he accepted a position to complete his MD at the Stanford University School of Medicine. While a medical student, Dr. Veeravagu worked with neurosurgery and the molecular imaging program to develop novel, non-invasive imaging tools and treatments for malignant neoplasms of central nervous system.

Dr. Veeravagu subsequently completed his neurosurgical residency at Stanford University. As a resident, Dr. Veeravagu was appointed by the President of the United States as a White House Fellow in 2012, serving as Special Assistant to Secretary of Defense Leon Panetta and Chuck Hagel to guide Department of Defense Policy on traumatic brain injury, spinal cord injury, and mental health treatment for the United States military. One of 14 people from around the nation to be selected, Dr. Veeravagu served as a speech writer, national security advisor, and health consultant directly to the Secretary of Defense.

After completion of his neurosurgical residency, Dr. Veeravagu was awarded the prestigious Neurosurgical Research and Education Foundation Post-Residency Clinical Fellowship Grant and completed his fellowship training in minimally invasive and complex deformity spine at Stanford University with both neurosurgical and orthopeadic training. Dr. Veeravagu also completed a clinical scholar rotation at the University of Miami Miller School of Medicine focused on endoscopic and robotic spine surgery.

Dr. Veeravagu’s research efforts are focused on the utilization of large national databases to assess cost, quality, and effectiveness of various treatment alogirthms as well as predictive analytics. Dr. Veeravagu is also an author and writes about current events, health policy, and public health-related topics for the San Francisco Chronicle, The Daily Beast, The BBC, and the Huffington Post.

Research & Scholarship

Current Research and Scholarly Interests

The focus of my laboratory is to utilize precision medicine techniques to improve the diagnosis and treatment of neurologic conditions. From traumatic brain injury to spinal scoliosis, the ability to capture detailed data regarding clinical symptoms and treatment outcomes has empowered us to do better for patients. Utilize data to do better for patients, that’s what we do.

Clinical Trials

Dexamethasone With or Without Thalidomide in Treating Patients With Newly Diagnosed Multiple MyelomaNot Recruiting

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing
so they stop growing or die. Thalidomide may stop the growth of cancer by stopping blood flow
to the tumor. Combining dexamethasone and thalidomide may kill more cancer cells. It is not
yet known whether dexamethasone is more effective with or without thalidomide in treating
multiple myeloma.
PURPOSE: Randomized phase III trial to determine the effectiveness of dexamethasone with or
without thalidomide in treating patients who have multiple myeloma.

Abstract

OF BACKGROUND DATA: Primary osseous spinal neoplasms (POSNs) include locally aggressive tumors such as osteosarcoma, chondrosarcoma, Ewing sarcoma, and chordoma. For such tumors, surgical resection is associated with improved survival for patients. Socioeconomic predictors of receiving surgery, however, have not been studied.OBJECTIVE: To examine the independent effect of race on receiving surgery and survival probability in patients with POSN.STUDY DESIGN: A total of 1904 patients from the SEER program at the National Cancer Institute database, all diagnosed with POSN of the spinal cord, vertebral column, pelvis, or sacrum from 2003 through 2012 were included in the study. Race was reported as white or nonwhite. Treatment included receiving surgery and no surgery.MATERIALS AND METHODS: Multivariable logistic regression was used to determine odds of receiving surgery based on race. Survival probability based on and race and surgery status was analyzed by Cox proportional hazards model and Kaplan-Meir curves. Results were adjusted for age at diagnosis, sex, socioeconomic status (composite index), tumor size, and tumor grade. Data were analyzed with SAS version 9.4.RESULTS: The study found that white patients were significantly more likely to receive surgery (odds ratio=3.076, P<0.01). Furthermore, nonwhite race was associated with significantly shorter survival time [hazard ratio (HR)=1.744, P<0.05]. Receiving surgery was associated with improved overall survival (HR=2.486, P<0.01). After adjusting for receiving surgery, white race remained significantly associated with higher survival probability (HR=2.061, P<0.05).CONCLUSIONS: This national study of patients with typically aggressive POSN found a significant correlation between race and the likelihood of receiving surgery. The study also found race to be a significant predictor of overall survival, regardless of receiving surgical treatment. These findings suggest an effect of race on receiving treatment and survival in patients with POSN, regardless of socioeconomic status. Further studies are required to understand reasons underlying these findings, and how they may be addressed.

Abstract

Spine surgery is a key target for cost reduction within the United States health care system. One possible strategy involves the transition of inpatient surgeries to the ambulatory setting. Lumbar laminectomy with or without discectomy, lumbar fusion, anterior cervical discectomy and fusion, and cervical disc arthroplasty all represent promising candidates for outpatient surgeries in select populations. In this focused review, the authors clarify the different definitions used in studies describing outpatient spine surgery. They also discuss the body of evidence supporting each of these procedures and summarize the proposed cost savings. Finally, they examine several patient- and surgeon-specific considerations to highlight the barriers in translating outpatient spine surgery into actual practice.

Abstract

OBJECTIVE There has been considerable debate about the utility of the operating microscope in lumbar discectomy and its effect on outcomes and cost. METHODS A commercially available longitudinal database was used to identify patients undergoing discectomy with or without use of a microscope between 2007 and 2015. Propensity matching was performed to normalize differences between demographics and comorbidities in the 2 cohorts. Outcomes, complications, and cost were subsequently analyzed using bivariate analysis. RESULTS A total of 42,025 patients were identified for the "macroscopic" group, while 11,172 patients were identified for the "microscopic" group. For the propensity-matched analysis, the 11,172 patients in the microscopic discectomy group were compared with a group of 22,340 matched patients who underwent macroscopic discectomy. There were no significant differences in postoperative complications between the groups other than a higher proportion of deep vein thrombosis (DVT) in the macroscopic discectomy cohort versus the microscopic discectomy group (0.4% vs 0.2%, matched OR 0.48 [95% CI 0.26-0.82], p = 0.0045). Length of stay was significantly longer in the macroscopic group compared to the microscopic group (mean 2.13 vs 1.83 days, p < 0.0001). Macroscopic discectomy patients had a higher rate of revision surgery when compared to microscopic discectomy patients (OR 0.92 [95% CI 0.84-1.00], p = 0.0366). Hospital charges were higher in the macroscopic discectomy group (mean $19,490 vs $14,921, p < 0.0001). CONCLUSIONS The present study suggests that the use of the operating microscope in lumbar discectomy is associated with decreased length of stay, lower DVT rate, lower reoperation rate, and decreased overall hospital costs.

Abstract

The role of arthrodesis in the surgical management of lumbar spondylolisthesis remains controversial. We hypothesized that practice patterns and outcomes for this patient population may vary widely.To characterize geographic variation in surgical practices and outcomes for patients with lumbar spondylolisthesis.Retrospective analysis on a national longitudinal database between 2007 and 2014.We calculated arthrodesis rates, inpatient and long term costs, and key quality indicators (e.g. reoperation rates). Using linear and logistic regression models, we then calculated expected quality indicator values, adjusting for patient-level demographic factors, and compared these values to the observed values, to assess quality variation apart from differences in patient populations.We identified a cohort of 67,077 patients (60.7% female, mean age of 59.8 years (SD, 12.0) with lumbar spondylolisthesis who received either laminectomy or laminectomy with arthrodesis. The majority of patients received arthrodesis (91.8%). Actual rates of arthrodesis varied from 97.5% in South Dakota to 81.5% in Oregon. Geography remained a significant predictor of arthrodesis even after adjusting for demographic factors (p<0.001). Marked geographic variation was also observed in initial costs ($32,485 in Alabama to $78,433 in Colorado), two-year post-operative costs ($15,612 in Arkansas to $34,096 in New Jersey), length of hospital stay (2.6 days in Arkansas to 4.5 in Washington, D.C.), 30-day complication rates (9.5% in South Dakota to 22.4% in Maryland), 30-day readmission rates (2.5% in South Dakota to 13.6% in Connecticut), and reoperation rates (1.8% in Maine to 12.7% in Alabama).There is marked geographic variation in the rates of arthrodesis in treatment of spondylolisthesis within the United States. This variation remains pronounced after accounting for patient-level demographic differences. Costs of surgery and quality outcomes also vary widely. Further study is necessary to understand the drivers of this variation.

Abstract

Retrospective longitudinal cohort analysis of patients diagnosed in 2010, with continuous enrollment six months prior to and 12 months following the initial visit.To determine whether provider specialty influences patterns of opiate utilization long after initial diagnosis.Patients with low back pain present to a variety of providers and receive a spectrum of treatments, including opiate medications. The impact of initial provider type on opiate use in this population is uncertain.We performed a retrospective analysis of opiate-naïve adult patients in the United States with newly diagnosed low back or lower extremity pain. We estimated the risk of early opiate prescription (≤ 14 days from diagnosis) and long-term opiate use (≥ six prescriptions in 12 months) based on the provider type at initial diagnosis using multivariable logistic regression, adjusting for patient demographics and comorbidities.We identified 478,981 newly diagnosed opiate-naïve patients. Of these, 40.4% received an opiate prescription within one year and 4.0% met criteria for long-term use. The most common initial provider type was family practice, associated with a 24.4% risk of early opiate prescription (95% CI, 24.1-24.6) and a 2.0% risk of long-term opiate use (95% CI, 2.0-2.1). Risk of receiving an early opiate prescription was higher among patients initially diagnosed by emergency medicine (43.1%; 95% CI, 41.6-44.5) or at an urgent care facility (40.8%; 95% CI, 39.4-42.3). Risk of long-term opiate use was highest for patients initially diagnosed by pain management/anesthesia (6.7%; 95% CI, 6.0-7.3) or physical medicine and rehabilitation (3.4%; 95% CI, 3.1-3.8) providers.Initial provider type influences early opiate prescription and long-term opiate use among opiate-naïve patients with newly diagnosed low back and lower extremity pain.3.

Abstract

OBJECTIVE Pediatric spinal astrocytomas are rare spinal lesions that pose unique management challenges. Therapeutic options include gross-total resection (GTR), subtotal resection (STR), and adjuvant chemotherapy or radiation therapy. With no randomized controlled trials, the optimal management approach for children with spinal astrocytomas remains unclear. The aim of this study was to conduct a systematic review and meta-analysis on pediatric spinal astrocytomas. METHODS The authors performed a systematic review of the PubMed/MEDLINE electronic database to investigate the impact of histological grade and extent of resection on overall survival among patients with spinal cord astrocytomas. They retained publications in which the majority of reported cases included astrocytoma histology. RESULTS Twenty-nine previously published studies met the eligibility criteria, totaling 578 patients with spinal cord astrocytomas. The spinal level of intramedullary spinal cord tumors was predominantly cervical (53.8%), followed by thoracic (40.8%). Overall, resection was more common than biopsy, and GTR was slightly more commonly achieved than STR (39.7% vs 37.0%). The reported rates of GTR and STR rose markedly from 1984 to 2015. Patients with high-grade astrocytomas had markedly worse 5-year overall survival than patients with low-grade tumors. Patients receiving GTR may have better 5-year overall survival than those receiving STR. CONCLUSIONS The authors describe trends in the management of pediatric spinal cord astrocytomas and suggest a benefit of GTR over STR for 5-year overall survival.

Abstract

OBJECTIVE Preoperative depression has been linked to a variety of adverse outcomes following lumbar fusion, including increased pain, disability, and 30-day readmission rates. The goal of the present study was to determine whether preoperative depression is associated with increased narcotic use following lumbar fusion. Moreover, the authors examined the association between preoperative depression and a variety of secondary quality indicator and economic outcomes, including complications, 30-day readmissions, revision surgeries, likelihood of discharge home, and 1- and 2-year costs. METHODS A retrospective analysis was conducted using a national longitudinal administrative database (MarketScan) containing diagnostic and reimbursement data on patients with a variety of private insurance providers and Medicare for the period from 2007 to 2014. Multivariable logistic and negative binomial regressions were performed to assess the relationship between preoperative depression and the primary postoperative opioid use outcomes while controlling for demographic, comorbidity, and preoperative prescription drug-use variables. Logistic and log-linear regressions were also used to evaluate the association between depression and the secondary outcomes of complications, 30-day readmissions, revisions, likelihood of discharge home, and 1- and 2-year costs. RESULTS The authors identified 60,597 patients who had undergone lumbar fusion and met the study inclusion criteria, 4985 of whom also had a preoperative diagnosis of depression and 21,905 of whom had a diagnosis of spondylolisthesis at the time of surgery. A preoperative depression diagnosis was associated with increased cumulative opioid use (β = 0.25, p < 0.001), an increased risk of chronic use (OR 1.28, 95% CI 1.17-1.40), and a decreased probability of opioid cessation (OR 0.96, 95% CI 0.95-0.98) following lumbar fusion. In terms of secondary outcomes, preoperative depression was also associated with a slightly increased risk of complications (OR 1.14, 95% CI 1.03-1.25), revision fusions (OR 1.15, 95% CI 1.05-1.26), and 30-day readmissions (OR 1.19, 95% CI 1.04-1.36), although it was not significantly associated with the probability of discharge to home (OR 0.92, 95% CI 0.84-1.01). Preoperative depression also resulted in increased costs at 1 (β = 0.06, p < 0.001) and 2 (β = 0.09, p < 0.001) years postoperatively. CONCLUSIONS Although these findings must be interpreted in the context of the limitations inherent to retrospective studies utilizing administrative data, they provide additional evidence for the link between a preoperative diagnosis of depression and adverse outcomes, particularly increased opioid use, following lumbar fusion.

Abstract

Endoscopic discectomy and fusions have been gaining popularity in the recent past and are noted to be safe for their application in elderly population. The procedure involves ultra-small incision for discectomy followed by placement of percutaneous screws in awake patients. Treatment of advanced spinal pathology with endoscope-assisted techniques is challenging. Although not common with the endoscopic approach, postoperative infection can be problematic, as there are no established guidelines on its management.A 76-year-old female patient underwent lumbar 4-5 endoscopic-assisted transforaminal lumbar interbody fusion for severe degenerative changes leading to back and radicular leg pain. She did well postoperatively and was discharged home the following day. She presented to the outside hospital with new onset of severe back pain, sepsis, and positive methicillin-susceptible Staphylococcus aureus with blood culture and demonstrated no improvement while on antibiotics.Initial magnetic resonance imaging revealed postoperative changes only. With positive blood culture and localized pain, she was then offered to undergo a percutaneous drainage of the abscess. Under local anesthesia and intravenous sedation, a small pocket of collection was found along the endoscopic trajectory from previous surgery. After evacuation of the collection, the interbody device was irrigated with vancomycin through endoscope. Postoperatively, immediate symptomatic improvement was noted in back pain. She was discharged home on oxacillin and continues to do well at 12 months' follow-up with excellent fusion.The present case illustrates the successful treatment of a surgical-site infection after endoscope-assisted transforaminal lumbar interbody fusion via a repeat percutaneous endoscopic approach.

Abstract

To characterize cranioplasty complications and costs at a population level using a longitudinal national claims database.We identified cranioplasty patients between 2007-2014 in the MarketScan national database. We evaluated age, autograft usage, cranioplasty size, and cranioplasty timing on postoperative outcomes. We further analyzed associated costs. A subset analysis of adult cranioplasty patients with emergent indications, including stroke and trauma, was also performed.We identified 8,275 patients (mean 44.0±20.0 years, 45.2% male) consisting of 13.8% pediatric (<18 years), 76.0% adults (18-64 years), and 10.2% elderly adults (>65 years). Overall complication rate was 36.6%, mortality rate 0.5%, and 30-day readmission rate 12.0%. Elderly patients had the highest complication rate (p<0.0001). Overall, large cranioplasties (>5 cm) saw higher complication rates than small cranioplasties (≤5 cm, p=0.047). In those with emergent indications only(N=1,282), size did not influence complications-though large cranioplasties showed higher infection risk (p=0.02). Overall, autograft use did not affect outcomes, but was associated with higher complication risk-including infections-in the subset with only emergent indications (p<0.001, p=0.001). Late (>90 days) cranioplasty timing had higher complication rates in both the overall cohort and subset with emergent indications (p<0.001, p<0.001). Index costs of care were mainly driven by hospital payments in both the overall cohort and those with emergent indications.We found a high complication rate associated with cranioplasty in the U.S.A. Older age, large cranioplasties, and delayed cranioplasties increased complication risk overall. Among those with only emergent indications, complications were associated with a delayed time to cranioplasty and autograft usage.

Abstract

OBJECTIVE The ability to assess the risk of adverse events based on known patient factors and comorbidities would provide more effective preoperative risk stratification. Present risk assessment in spine surgery is limited. An adverse event prediction tool was developed to predict the risk of complications after spine surgery and tested on a prospective patient cohort. METHODS The spinal Risk Assessment Tool (RAT), a novel instrument for the assessment of risk for patients undergoing spine surgery that was developed based on an administrative claims database, was prospectively applied to 246 patients undergoing 257 spinal procedures over a 3-month period. Prospectively collected data were used to compare the RAT to the Charlson Comorbidity Index (CCI) and the American College of Surgeons National Surgery Quality Improvement Program (ACS NSQIP) Surgical Risk Calculator. Study end point was occurrence and type of complication after spine surgery. RESULTS The authors identified 69 patients (73 procedures) who experienced a complication over the prospective study period. Cardiac complications were most common (10.2%). Receiver operating characteristic (ROC) curves were calculated to compare complication outcomes using the different assessment tools. Area under the curve (AUC) analysis showed comparable predictive accuracy between the RAT and the ACS NSQIP calculator (0.670 [95% CI 0.60-0.74] in RAT, 0.669 [95% CI 0.60-0.74] in NSQIP). The CCI was not accurate in predicting complication occurrence (0.55 [95% CI 0.48-0.62]). The RAT produced mean probabilities of 34.6% for patients who had a complication and 24% for patients who did not (p = 0.0003). The generated predicted values were stratified into low, medium, and high rates. For the RAT, the predicted complication rate was 10.1% in the low-risk group (observed rate 12.8%), 21.9% in the medium-risk group (observed 31.8%), and 49.7% in the high-risk group (observed 41.2%). The ACS NSQIP calculator consistently produced complication predictions that underestimated complication occurrence: 3.4% in the low-risk group (observed 12.6%), 5.9% in the medium-risk group (observed 34.5%), and 12.5% in the high-risk group (observed 38.8%). The RAT was more accurate than the ACS NSQIP calculator (p = 0.0018). CONCLUSIONS While the RAT and ACS NSQIP calculator were both able to identify patients more likely to experience complications following spine surgery, both have substantial room for improvement. Risk stratification is feasible in spine surgery procedures; currently used measures have low accuracy.

Abstract

OBJECTIVE Recently, 2 surgeon rating websites (Consumers' Checkbook and ProPublica) were published to allow the public to compare surgeons through identifying surgeon volume and complication rates. Among neurosurgeons and orthopedic surgeons, only cervical and lumbar spine, hip, and knee procedures were included in this assessment. METHODS The authors examined the methodology of each website to assess potential sources of inaccuracy. Each online tool was queried for reports on neurosurgeons specializing in spine surgery and orthopedic surgeons specializing in spine, hip, or knee surgery. Surgeons were chosen from top-ranked hospitals in the US, as recorded by a national consumer publication ranking system, within the fields of neurosurgery and orthopedic surgery. The results were compared for accuracy and surgeon representation, and the results of the 2 websites were also compared. RESULTS The methodology of each site was found to have opportunities for bias and limited risk adjustment. The end points assessed by each site were actually not complications, but proxies of complication occurrence. A search of 510 surgeons (401 orthopedic surgeons [79%] and 109 neurosurgeons [21%]) showed that only 28% and 56% of surgeons had data represented on Consumers' Checkbook and ProPublica, respectively. There was a significantly higher chance of finding surgeon data on ProPublica (p < 0.001). Of the surgeons from top-ranked programs with data available, 17% were quoted to have high complication rates, 13% with lower volume than other surgeons, and 79% had a 3-star out of 5-star rating. There was no significant correlation found between the number of stars a surgeon received on Consumers' Checkbook and his or her adjusted complication rate on ProPublica. CONCLUSIONS Both the Consumers' Checkbook and ProPublica websites have significant methodological issues. Neither site assessed complication occurrence, but rather readmissions or prolonged length of stay. Risk adjustment was limited or nonexistent. A substantial number of neurosurgeons and orthopedic surgeons from top-ranked hospitals have no ratings on either site, or have data that suggests they are low-volume surgeons or have higher complication rates. Consumers' Checkbook and ProPublica produced different results with little correlation between the 2 websites in how surgeons were graded. Given the significant methodological issues, incomplete data, and lack of appropriate risk stratification of patients, the featured websites may provide erroneous information to the public.

Abstract

This is an updated version of the original Cochrane review published in 2013, Issue 4.Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG.To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG.The following electronic databases were searched in 2012 for the first version of the review: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to November week 3 2012), Embase (1980 to Week 46 2012). For this updated version, the following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 5), MEDLINE (Nov 2012 to June week 3 2016), Embase (Nov 2012 to 2016 week 26). All relevant articles were identified on PubMed and by using the 'related articles' feature. We also searched unpublished and grey literature including ISRCTN-metaRegister of Controled Trials, Physicians Data Query and ClinicalTrials.gov for ongoing trials.We planned to include patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT). Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression-free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL).A total of 1375 updated citations were searched and critically analyzed for relevance. This was undertaken independently by two review authors. The original electronic database searches yielded a total of 2764 citations. In total, 4139 citations have been critically analyzed for this updated review.No new RCTs of biopsy or resection for LGG were identified. No additional ineligible non-randomized studies (NRS) were included in this updated review. Twenty other ineligible studies were previously retrieved for further analysis despite not meeting the pre-specified criteria. Ten studies were retrospective or were literature reviews. Three studies were prospective, however they were limited to tumor recurrence and volumetric analysis and extent of resection. One study was a population-based parallel cohort in Norway, but not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was on high-grade gliomas (HGGs) and not LGG. Finally, one RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection.Since the last version of this review, no new studies have been identified for inclusion and currently there are no RCTs or CCTs available on which to base definitive clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Some retrospective studies and non-randomized prospective studies do seem to suggest improved OS and seizure control correlating to higher extent of resection. Future research could focus on RCTs to determine outcomes benefits for biopsy versus resection.

Abstract

Systematic review and meta-analysis.The aim of this study was to systematically evaluate the diagnostic utility of intraoperative neurophysiological monitoring (IONM) for detecting postoperative injury in resection of intramedullary spinal cord tumors (IMSCT).Surgical management of IMSCT can involve key neurological and vascular structures. IONM aims to assess the functional integrity of susceptible elements in real time. The diagnostic value of IONM for ISMCT has not been systematically evaluated.We performed a systematic review of the PubMed and MEDLINE databases for studies investigating the use of IONM for IMSCT and conducted a meta-analysis of diagnostic capability.Our search produced 257 citations. After application of exclusion criteria, 21 studies remained, 10 American Academy of Neurology grade III and 11 American Academy of Neurology grade IV. We found that a strong pooled mean sensitivity of 90% [95% confidence interval (CI), 84-94] and a weaker pooled mean specificity of 82% (95% CI, 70-90) for motor-evoked potential (MEP) recording changes. Somatosensory-evoked potential (SSEP) recording changes yielded pooled sensitivity of 85% (95% CI, 75-91) and pooled specificity of 72% (95% CI, 57-83). The pooled diagnostic odds ratio for MEP was 55.7 (95% CI, 26.3-119.1) and 14.3 (95% CI, 5.47-37.3) for SSEP. Bivariate analysis yielded summary receiver operative characteristic curves with area under the curve of 91.8% for MEPs and 86.3% for SSEPs.MEPs and SSEPs appear to be more sensitive than specific for detection of postoperative injury. Patients with perioperative neurological deficits are 56 times more likely to have had changes in MEPs during the procedure. We observed considerable variability in alarm criteria and interventions in response to IONM changes, indicating the need for prospective studies capable of defining standardized alarm criteria and responses.

Abstract

Spontaneous intrauterine depressed skull fractures (IDSF) are rare fractures that often require neurosurgical evaluation and therapy. The majority of reported congenital depressions are secondary to maternal abdominal trauma or instrumentation during delivery. Spontaneous IDSF occur in the setting of uneventful normal spontaneous vaginal delivery (NSVD) or cesarean section, without obvious predisposing risk factors. The etiology and optimal management of spontaneous IDSF remain controversial.We describe 2 cases of spontaneous IDSF that underwent cranioplasty at our institution using an absorbable mesh, as well as review the current state of knowledge regarding the diagnosis and management of spontaneous IDSF. The 2 neonates, 1 male and 1 female, presented at Lucile Packard Children's Hospital with spontaneous IDSF after uneventful NSVDs. The fractures were located in the left frontal and right parieto-temporal calvarium, respectively. Both patients underwent open craniotomy and elevation of their IDSF with mesh cranioplasty. At last follow-up, both patients were normocephalic and neurologically intact.Neurosurgery consultation is necessary for initial evaluation of spontaneous IDSF. Surgical intervention is indicated for larger defects and/or intracranial involvement. Expectant management and negative-pressure elevation have also been shown to be effective.

Abstract

OBJECTIVE Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making. METHODS A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS. RESULTS Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%-40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated. CONCLUSIONS SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.

Abstract

Cervical laminoplasty is an important alternative to laminectomy in decompressing of the cervical spine. Further evidence to assess the utility of laminoplasty is required. We examine outcomes of cervical laminoplasty via a population level analysis in the United States.We performed a population-level analysis using the national MarketScan longitudinal database to analyze outcomes and costs of cervical laminoplasty between 2007 and 2014. Outcomes included postoperative complications, revision rates, and functional outcomes.Using a national administrative database, we identified 2613 patients (65.6% male, mean 58.5 years) who underwent cervical laminoplasty. Mean length of stay was 3.1 ± 2.8 days and mean follow-up was 795.5 ± 670.6 days. The overall complication rate was 22.5% (N = 587), 30-day readmission rate was 7.5% (N = 195), and mortality rate was 0.08% (N = 2, elderly patients only). The complication rate was significantly increased in elderly patients (age >65 years) compared to non-elderly patients (OR 0.751, p

Abstract

Retrospective analysis on a national longitudinal database (2007-2014).To determine the association between arthrodesis and complication rates, costs, surgical revision, and postoperative opioid prescription.Arthrodesis in patients receiving laminectomy for lumbar spondylolisthesis remains controversial. However, population-level evidence to support the use of arthrodesis remains limited.We identified 73,176 patient records and used coarsened exact matching to create comparable populations of patients who received laminectomy or laminectomy with arthrodesis. We use linear and logistic regression models to analyze the relationship between arthrodesis and postoperative complications, length of stay, costs, readmissions, surgical revisions, and postoperative opioid prescribing.Patients who underwent arthrodesis spent one more day in the hospital on average (p

Abstract

The evidence base for many neurosurgical procedures has been limited. We performed a comprehensive and systematic analysis of study design, quality of reporting, and trial results of neurosurgical randomized controlled trials (RCTs).To systematically assess the design and quality characteristics of neurosurgical RCTs.From January 1961 to June 2016, RCTs with >5 patients assessing any 1 neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library.The median sample size in the 401 eligible RCTs was 73 patients with a mean patient age of 49.6. Only 111 trials (27.1%) described allocation concealment, 140 (34.6%) provided power calculations, and 117 (28.9%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 226 reports (56.4%), no difference between the procedures was found in 166 trials (41.4%), and significant harm was reported in 9 trials (2.2%). Trials with a larger sample size were more likely to report randomization mode, specify allocation concealment, and power calculations (all P < .001). Government funding was associated with better specification of power calculations ( P = .008) and of allocation concealment ( P = .026), while industry funding was associated with reporting significant efficacy ( P = .02). Reporting of funding, specification of randomization mode and primary outcomes, and mention of power calculations improved significantly (all, P < .05) over time.Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.

Abstract

Osteochondromas are the most frequent benign bone tumors but only rarely occur along the spinal column and even more rarely induce symptoms from spinal cord compression.We report 2 adult patients, both with a history of hereditary multiple exostoses, who presented with cervical myelopathy secondary to osteochondromas. The first patient is a 22-year-old man with numbness and weakness of his right upper limb and neck pain. Radiologic images showed a bony tumor arising from the C3 lamina with evidence of severe spinal cord compression. The second patient is a 20-year-old woman with weakness of her left upper and lower limbs and progressive numbness of the left hand, as well as neck and back pain. Radiologic images showed a bony tumor arising from the C4 lamina with evidence of significant spinal cord compression and cord signal abnormality. Both patients underwent surgical excision of the epidural mass and pathology confirmed a diagnosis of osteochondroma.We discuss the role of surgical intervention, management, and postoperative follow-up in adult patients with cervical osteochondromas. Recommended management includes radiographic imaging and surgical intervention, particularly when evidence of spinal cord impingement occurs. Consistent postoperative follow-up is necessary to ensure appropriate recovery of neurologic function. Surgical management of cervical osteochondromas typically results in excellent and stable clinical outcomes with rare recurrence.

Abstract

Intra-operative MRI (ioMRI) may be used to optimize tumor resection. Utilization of this technology allows for the removal of residual tumor mass following initial tumor removal, maximizing the extent of resection. This, in turn, has been shown to lead to improved outcomes. Individual studies have examined the impact of ioMRI on the rate of extended resection, but a comprehensive review of this topic is needed. A literature review of the MEDLINE, EMBASE, CENTRAL, and Google Scholar databases revealed 12 eligible studies. This included 804 primary operations and 238 extended resections based on ioMRI findings. Use of ioMRI led to extended tumor resection in 13.3-54.8% of patients (mean 37.3%). Stratification by tumor type showed additional resection occurred, on average, in 39.1% of glioma resections (range 13.3-70.0%), 23.5% of pituitary tumor resections (range 13.3-33.7%), and 35.0% of nonspecific tumor resections (range 17.5-40%). Tumor type (glioma vs. pituitary) did not significantly influence the rate of further excision following ioMRI (p=0.309). There was no difference in secondary resection rate between studies limited to pediatric patients and those including adults (p=0.646). Thus, the use of intra-operative MRI frequently results in further resection of tumors. It is primarily used for the resection of gliomas and pituitary tumors. Tumor type does not appear to be a significant contributing factor to the rate of secondary tumor removal. Limited evidence suggests that extended resection may translate into improved clinical outcomes and mortality rates. However, results have not been unanimous, while clinical effect sizes have often been modest.

Abstract

Osteochondromas are the most frequent benign bone tumors but only rarely occur along the spinal column and even more rarely induce symptoms from spinal cord compression.We report 2 adult patients, both with a history of hereditary multiple exostoses, who presented with cervical myelopathy secondary to osteochondromas. The first patient is a 22-year-old man with numbness and weakness of his right upper limb and neck pain. Radiologic images showed a bony tumor arising from the C3 lamina with evidence of severe spinal cord compression. The second patient is a 20-year-old woman with weakness of her left upper and lower limbs and progressive numbness of the left hand, as well as neck and back pain. Radiologic images showed a bony tumor arising from the C4 lamina with evidence of significant spinal cord compression and cord signal abnormality. Both patients underwent surgical excision of the epidural mass and pathology confirmed a diagnosis of osteochondroma.We discuss the role of surgical intervention, management, and postoperative follow-up in adult patients with cervical osteochondromas. Recommended management includes radiographic imaging and surgical intervention, particularly when evidence of spinal cord impingement occurs. Consistent postoperative follow-up is necessary to ensure appropriate recovery of neurologic function. Surgical management of cervical osteochondromas typically results in excellent and stable clinical outcomes with rare recurrence.

Abstract

Propensity score matched retrospective study using a nationwide longitudinal database.To quantify the longitudinal economic impact of venous thromboembolism (VTE) complications in spinal fusion patients.VTE is a rare and serious complication that may occur after spine surgery. The long-term socioeconomic impact understanding of these events has been limited by small sample sizes and a lack of longitudinal follow-up. We provide a comparative economic outcomes analysis of these complications.We identified 204,308 patients undergoing spinal fusion procedures in a national billing claims database (MarketScan) between 2006 and 2010. Cohorts were balanced using 50:1 propensity score matching and outcome measures compared at 6, 12, and 18 months postoperation.A total of 1196 (0.6%) patients developed postoperative VTE, predominantly occurring following lumbar fusion (69.7%). Postoperative VTE patients demonstrated an increase in hospital length of stay (7.8 vs. 3.3 d, P<0.001) and a decreased likelihood of being discharged home (71% vs. 85%, P<0.001). A $26,306 increase in total hospital payments (P<0.001) was observed, with a disproportionate increase seen in hospital payments ($22,103, P<0.001), relative to physician payments ($1766, P=0.001).At 6, 12, and 18 months postfusion, increased rates of readmission and follow-up clinic visits were observed. Delayed readmissions were associated with decreased length of stay (3.6 vs. 4.6 d, P<0.001), but increased total payments, averaging at $21,270 per readmission. VTE patients generated greater cumulative outpatient service payments, costing $8075, $11,134, and $13,202 more at 6, 12, and 18 months (P<0.001).VTEs are associated with longer hospitalizations, a decreased likelihood of being discharged home, and overall increases of hospital resource utilization and cost in inpatient and outpatient settings. VTE patients generate greater charges in the outpatient setting and are more likely to become readmitted at 6, 12, and 18 months after surgery, demonstrating a significant socioeconomic impact long after occurrence.Level III-therapeutic.

Abstract

OBJECTIVE Recently, 2 surgeon rating websites (Consumers' Checkbook and ProPublica) were published to allow the public to compare surgeons through identifying surgeon volume and complication rates. Among neurosurgeons and orthopedic surgeons, only cervical and lumbar spine, hip, and knee procedures were included in this assessment. METHODS The authors examined the methodology of each website to assess potential sources of inaccuracy. Each online tool was queried for reports on neurosurgeons specializing in spine surgery and orthopedic surgeons specializing in spine, hip, or knee surgery. Surgeons were chosen from top-ranked hospitals in the US, as recorded by a national consumer publication ranking system, within the fields of neurosurgery and orthopedic surgery. The results were compared for accuracy and surgeon representation, and the results of the 2 websites were also compared. RESULTS The methodology of each site was found to have opportunities for bias and limited risk adjustment. The end points assessed by each site were actually not complications, but proxies of complication occurrence. A search of 510 surgeons (401 orthopedic surgeons [79%] and 109 neurosurgeons [21%]) showed that only 28% and 56% of surgeons had data represented on Consumers' Checkbook and ProPublica, respectively. There was a significantly higher chance of finding surgeon data on ProPublica (p < 0.001). Of the surgeons from top-ranked programs with data available, 17% were quoted to have high complication rates, 13% with lower volume than other surgeons, and 79% had a 3-star out of 5-star rating. There was no significant correlation found between the number of stars a surgeon received on Consumers' Checkbook and his or her adjusted complication rate on ProPublica. CONCLUSIONS Both the Consumers' Checkbook and ProPublica websites have significant methodological issues. Neither site assessed complication occurrence, but rather readmissions or prolonged length of stay. Risk adjustment was limited or nonexistent. A substantial number of neurosurgeons and orthopedic surgeons from top-ranked hospitals have no ratings on either site, or have data that suggests they are low-volume surgeons or have higher complication rates. Consumers' Checkbook and ProPublica produced different results with little correlation between the 2 websites in how surgeons were graded. Given the significant methodological issues, incomplete data, and lack of appropriate risk stratification of patients, the featured websites may provide erroneous information to the public.

Abstract

Retrospective database analysis.To examine the impact of training pathway, either neurosurgical or orthopedic, on complications, readmissions, and revisions in spine surgery.Training pathway has been shown to have an impact on outcomes in various surgical subspecialties. Although training pathway has not been shown to have a significant impact on spine surgery outcomes in the perioperative period, long-term results are unknown.A retrospective analysis of 197,682 patients receiving 1 of 3 common spine surgeries [lumbar laminectomy, lumbar fusion, and anterior cervical discectomy and fusion (ACDF)] between 2006 and 2010 was conducted. Patient data were obtained from a large claims database. Postoperative adverse effects, all-cause readmission, revision surgery rates, and intermediary payments in these cohorts of patients were compared between spine surgeons with either neurosurgical or orthopedic backgrounds.Patient demographics, hospital-stay characteristics, and medical comorbidities were similar between neurosurgeons and orthopedic surgeons. The risks of surgical complications, all-cause readmission, and revision surgery were also similar between neurosurgeons and orthopedic surgeons across all procedure types assessed, with several minor exceptions: neurosurgeons had marginally higher odds of any complication for lumbar fusions [odds ratio (OR) 1.14; 95% confidence interval (CI), 1.09-1.20] and ACDFs (OR, 1.09; 95% CI, 1.04-1.15). Neurosurgeons also had slightly higher rates of revision surgery for concurrent lumbar laminectomy with fusion (OR, 1.14; 95% CI, 1.08-1.22), and ACDFs (OR, 1.20; 95% CI, 1.14-1.28). No associations between surgeon type and any particular complication were consistently observed for all procedure groups. There were also no associations between surgeon type and 30-day all-cause readmission. Median total intermediary payments were somewhat higher for neurosurgery patients for all procedure groups assessed.Few significant associations between surgeon type and patient outcomes exist in the context of spine surgery. Those which do are small and unlikely to be clinically meaningful.Level 3.

Abstract

Retrospective study using the MarketScan longitudinal database (2006-2010).Compare complication rates between groups of patients undergoing anterior cervical discectomy and fusion (ACDF) procedures performed by surgeons with high versus low mean annual ACDF volume.Over the past decade the volume of ACDFs performed has increased, concurrent with greater appreciation of potential for associated complications. The effect of surgeon procedure volume on adverse events occurrence in the post-operative period has not been described.We evaluated the relationship between surgeon procedure volume and post-operative incidence of any complication using a multivariate logistic regression model. 24,461 patients undergoing single and multiple level ACDFs were identified in the MarketScan database by Current Procedural Terminology coding. Annual surgeon volume was determined by tracking of anonymized surgeon identification numbers, with high-volume surgeons defined as those performing an average of at least 30 ACDF procedures annually.Over 50% of unique surgeon identifiers reported less than 9 ACDF operations per year, while the highest decile reported a range of 44 to 101. High surgeon volume was protective for any complication (OR.72, 95% CI 0.65-0.81 P<0.0001), with an adjusted number needed to harm of 44. Patients treated by high-volume physicians specifically had lower odds of dysphagia (2.22% vs. 3.08%, OR 0.71, P<0.0013), neurological complications (0.33% vs. 0.64%, OR 0.52, P<0.0107), new diagnosis of chronic pain (0.48% vs. 0.82%, OR 0.58, P<0.0119), pulmonary complications (1.10% vs. 1.58%, OR 0.69, P<0.0138), and other wound complications (0.06% vs. 0.22%, OR 0.28, P<0.0242).We demonstrate a possible association between higher surgeon procedure volume and decreased post-operative complications following anterior cervical discectomy and fusion. There was no difference observed in need for revision surgery or readmission rates.

Abstract

Total hip arthroplasty (THA) is an established treatment for end-stage arthritis, congenital deformity, and trauma with good long-term clinical and functional outcomes. Delayed sciatic nerve injury is a rare complication after THA that requires prompt diagnosis and management.We present a case of sciatic nerve motor and sensory deficit in a 52-year-old patient 2 years after index left THA. Electromyography (EMG) results and imaging with radiographs and CT of the affected hip demonstrated an aberrant acetabular cup screw in the posterior-inferior quadrant adjacent to the sciatic nerve.The patient underwent surgical exploration that revealed injury to the peroneal division of the sciatic nerve due to direct injury from screw impingement. A literature review identified 11 patients with late-onset neuropathy after THA. Ten patients underwent surgical exploration and pain often resolved after surgery with 56% of patients recovering sensory function and 25% experiencing full recovery of motor function.Delayed neuropathy of the sciatic nerve is a rare complication after THA that is most often due to hardware irritation, component failure, or wear-related pseudotumor formation. Operative intervention is often pursued to explore and directly visualize the nerve with limited results in the literature showing modest relief of pain and sensory symptoms and poor restoration of motor function.

Abstract

OBJECTIVE The authors performed a population-based analysis of national trends, costs, and outcomes associated with cervical spondylotic myelopathy (CSM) in the United States. They assessed postoperative complications, resource utilization, and predictors of costs, in this surgically treated CSM population. METHODS MarketScan data (2006-2010) were used to retrospectively analyze the complications and costs of different spine surgeries for CSM. The authors determined outcomes following anterior cervical discectomy and fusion (ACDF), posterior fusion, combined anterior/posterior fusion, and laminoplasty procedures. RESULTS The authors identified 35,962 CSM patients, comprising 5154 elderly (age ≥ 65 years) patients (mean 72.2 years, 54.9% male) and 30,808 nonelderly patients (mean 51.1 years, 49.3% male). They found an overall complication rate of 15.6% after ACDF, 29.2% after posterior fusion, 41.1% after combined anterior and posterior fusion, and 22.4% after laminoplasty. Following ACDF and posterior fusion, a significantly higher risk of complication was seen in the elderly compared with the nonelderly (reference group). The fusion level and comorbidity-adjusted ORs with 95% CIs for these groups were 1.54 (1.40-1.68) and 1.25 (1.06-1.46), respectively. In contrast, the elderly population had lower 30-day readmission rates in all 4 surgical cohorts (ACDF, 2.6%; posterior fusion, 5.3%; anterior/posterior fusion, 3.4%; and laminoplasty, 3.6%). The fusion level and comorbidity-adjusted odds ratios for 30-day readmissions for ACDF, posterior fusion, combined anterior and posterior fusion, and laminoplasty were 0.54 (0.44-0.68), 0.32 (0.24-0.44), 0.17 (0.08-0.38), and 0.39 (0.18-0.85), respectively. CONCLUSIONS The authors' analysis of the MarketScan database suggests a higher complication rate in the surgical treatment of CSM than previous national estimates. They found that elderly age (≥ 65 years) significantly increased complication risk following ACDF and posterior fusion. Elderly patients were less likely to experience a readmission within 30 days of surgery. Postoperative complication occurrence, and 30-day readmission were significant drivers of total cost within 90 days of the index surgical procedure.

Abstract

Postoperative metrics are increasingly important in determining standards of quality for physicians and hospitals. Although complications following spinal surgery have been described, procedural and patient variables have yet to be incorporated into a predictive model of adverse-event occurrence. We sought to develop a predictive model of complication occurrence after spine surgery.We used longitudinal prospective data from a national claims database and developed a predictive model incorporating complication type and frequency of occurrence following spine surgery procedures. We structured our model to assess the impact of features such as preoperative diagnosis, patient comorbidities, location in the spine, anterior versus posterior approach, whether fusion had been performed, whether instrumentation had been used, number of levels, and use of bone morphogenetic protein (BMP). We assessed a variety of adverse events. Prediction models were built using logistic regression with additive main effects and logistic regression with main effects as well as all 2 and 3-factor interactions. Least absolute shrinkage and selection operator (LASSO) regularization was used to select features. Competing approaches included boosted additive trees and the classification and regression trees (CART) algorithm. The final prediction performance was evaluated by estimating the area under a receiver operating characteristic curve (AUC) as predictions were applied to independent validation data and compared with the Charlson comorbidity score.The model was developed from 279,135 records of patients with a minimum duration of follow-up of 30 days. Preliminary assessment showed an adverse-event rate of 13.95%, well within norms reported in the literature. We used the first 80% of the records for training (to predict adverse events) and the remaining 20% of the records for validation. There was remarkable similarity among methods, with an AUC of 0.70 for predicting the occurrence of adverse events. The AUC using the Charlson comorbidity score was 0.61. The described model was more accurate than Charlson scoring (p < 0.01).We present a modeling effort based on administrative claims data that predicts the occurrence of complications after spine surgery.We believe that the development of a predictive modeling tool illustrating the risk of complication occurrence after spine surgery will aid in patient counseling and improve the accuracy of risk modeling strategies.

Abstract

Recent advancements in stem cell biology and neuromodulation have ushered in a battery of new neurorestorative therapies for ischemic stroke. While the understanding of stroke pathophysiology has matured, the ability to restore patients' quality of life remains inadequate. New therapeutic approaches, including cell transplantation and neurostimulation, focus on reestablishing the circuits disrupted by ischemia through multidimensional mechanisms to improve neuroplasticity and remodeling. The authors provide a broad overview of stroke pathophysiology and existing therapies to highlight the scientific and clinical implications of neurorestorative therapies for stroke.

Abstract

Avulsion of the abducens nerve in the setting of geniculate ganglion injury after temporal bone fracture is unreported previously. We discuss clinical assessment and management of a patient with traumatic avulsion of cranial nerve (CN) VI in the setting of an ipsilateral CN VII injury after temporal bone fracture and call attention to this unusual injury.A 26-year-old man suffered a temporal bone fracture after a motor vehicle accident and developed diplopia and right-sided facial droop. Six weeks after the accident, the patient was readmitted with worsening diplopia and ipsilateral facial weakness. He demonstrated absent lateral gaze on the right suggestive of either restrictive movement or right.In addition, he had right-sided facial palsy graded as 6/6 House-Brackmann. High-resolution computed tomography demonstrated a right-sided longitudinal otic capsule-sparing temporal bone fracture that propagated into the facial nerve canal and geniculate fossa. Magnetic resonance imaging revealed discontinuity of the right CN VI between the pons and the Dorello canal, as well as injury to the ipsilateral geniculate ganglion. CN VII was intact proximally, from the pons through the internal auditory canal. Consensus was reached to proceed with conservative management. At 13 months after injury, the patient reported 1/6 House-Brackmann with no improvement in CN VI function.This case illustrates 2 subtle findings on imaging with potential therapeutic implications, notably the role of surgical intervention for facial nerve palsy.

Abstract

Few neurologic diseases have captured the nation's attention more completely than chronic traumatic encephalopathy (CTE), which has been discovered in the autopsies of professional athletes, most notably professional football players. The tragic case of Junior Seau, a Hall of Fame, National Football League linebacker, has been the most high-profile confirmed case of CTE. Here we describe Seau's case, which concludes an autopsy conducted at the National Institutes of Health that confirmed the diagnosis.Since 1990, Junior Seau had a highly distinguished 20-year career playing for the National Football League as a linebacker, from which he sustained multiple concussions. He committed suicide on May 2, 2012, at age 43, after which an autopsy confirmed a diagnosis of CTE. His clinical history was significant for a series of behavioral disturbances. Seau's history and neuropathologic findings were used to better understand the pathophysiology, diagnosis, and possible risk factors for CTE.This high-profile case reflects an increasing awareness of CTE as a long-term consequence of multiple traumatic brain injuries. The previously unforeseen neurologic risks of American football have begun to cast doubt on the safety of the sport.

Abstract

Few neurosurgeons practicing today have had training in the field of endoscopic spine surgery during residency or fellowship. Nevertheless, over the past 40 years individual spine surgeons from around the world have worked to create a subfield of minimally invasive spine surgery that takes the point of visualization away from the surgeon's eye or the lens of a microscope and puts it directly at the point of spine pathology. What follows is an attempt to describe the story of how endoscopic spine surgery developed and to credit some of those who have been the biggest contributors to its development.

Abstract

Postoperative visual loss (POVL) is a potentially devastating complication of lumbar spine surgery that may lead to significant functional impairment. Although POVL is rare, a review of the literature shows that it is being reported with increasing frequency. A systematic analysis detailing the etiology and prognosis of the 3 main types of POVL has yet to be published. We reviewed potential preoperative and intraoperative risk factors for ischemic optic neuropathy (ION), central retinal artery occlusion (CRAO), and cortical blindness (CB) after lumbar spine surgery.A PubMed and Google literature search was completed in the absence of time constraints. Relevant articles on POVL after spine surgery were identified and reviewed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.We identified 4 large-scale studies that statistically analyzed risk factors for POVL. ION, CRAO, and CB were the most frequently reported POVL types in the literature. Data were abstracted from 19 ION case reports, 3 CRAO case reports, and 5 CB case reports.We reviewed the preoperative and intraoperative risk factors for each of the 3 main POVL types, using several published case reports to supplement the limited large-scale studies available. ION risks may be influenced by a longer operative time in the prone position with anemia, hypotension, and blood transfusion. The risk for CRAO is usually due to improper positioning during the surgery. Prone positioning and obesity were found to be most commonly associated with CB development. The prognosis, prevention techniques, and treatment of each POVL type can vary considerably.

Abstract

We sought to describe complications after resection for meningioma with the use of longitudinal administrative data, which our group has shown recently to be superior to nonlongitudinal administrative data.We identified patients who underwent resection for meningioma between 2010 and 2012 in the Thomson Reuters MarketScan database. Current Procedural Terminology coding at inpatient visit was used to select for meningioma resection procedure. Comorbidities and complications were obtained by use of the International Classification of Diseases, Ninth Revision or Current Procedural Terminology coding. Associations between complications and demographic and clinical factors were evaluated with logistic regression.We identified a total of 2216 patients. Approximately 41% developed 1 or more perioperative complications. Approximately 15% were readmitted within 30 days of their procedure. The most frequent complications that occurred in our cohort were new postoperative seizures (11.8%), postoperative dysrhythmia (7.9%), intracranial hemorrhage (5.9%), and cerebral artery occlusion (5.4%). General neurosurgical complications and general neurologic complications occurred in 4.4% and 16.1% of patients, respectively. Nearly 55% of elderly patients (≥ 70 years) developed 1 or more perioperative complication (vs. 39% of nonelderly patients). After we adjusted for comorbidities, elderly status and male sex were found to be significantly associated with increased odds for a variety of complications.In this study, we report complication rates in patients undergoing resection for meningioma. Because of the longitudinal nature of the MarketScan database, we were able to capture a wide array of specific postoperative complications associated with meningioma resection procedures. Care should be taken in the selection of candidates for meningioma resection.

Abstract

The significant medical and economic tolls of spinal disorders, increasing volume of spine surgeries, and focus on quality metrics have made it imperative to understand postoperative complications. This study demonstrates the utility of a longitudinal administrative database for capturing overall and procedure-specific complication rates after various spine surgery procedures.The Thomson Reuters MarketScan Commercial Claims and Encounters and the Medicare Supplemental and Coordination of Benefits database was used to conduct a retrospective analysis of longitudinal administrative data from a sample of approximately 189,000 patients. Overall and procedure-specific complication rates at 5 time points ranging from immediately postoperatively (index) to 30 days postoperatively were computed.The results indicated that the frequency of individual complication types increased at different rates. The overall complication rate including all spine surgeries was 13.6% at the index time point and increased to 22.8% at 30 days postoperatively. The frequencies of wound dehiscence, infection, and other wound complications exhibited large increases between 10 and 20 days postoperatively, while complication rates for new chronic pain, delirium, and dysrhythmia increased more gradually over the 30-day period studied. When specific surgical procedures were considered, 30-day complication rates ranged from 8.6% in single-level anterior cervical fusions to 27.3% in multilevel combined anterior and posterior lumbar spine fusions.This study demonstrates the usefulness of a longitudinal administrative database in assessing postoperative complication rates after spine surgery. Use of this database gave results that were comparable to those in prospective studies and superior to those obtained with nonlongitudinal administrative databases. Longitudinal administrative data may improve the understanding of overall and procedure-specific complication rates after spine surgery.

Abstract

The significant medical and economic tolls of spinal disorders, increasing volume of spine surgeries, and focus on quality metrics have made it imperative to understand postoperative complications. This study demonstrates the utility of a longitudinal administrative database for capturing overall and procedure-specific complication rates after various spine surgery procedures.The Thomson Reuters MarketScan Commercial Claims and Encounters and the Medicare Supplemental and Coordination of Benefits database was used to conduct a retrospective analysis of longitudinal administrative data from a sample of approximately 189,000 patients. Overall and procedure-specific complication rates at 5 time points ranging from immediately postoperatively (index) to 30 days postoperatively were computed.The results indicated that the frequency of individual complication types increased at different rates. The overall complication rate including all spine surgeries was 13.6% at the index time point and increased to 22.8% at 30 days postoperatively. The frequencies of wound dehiscence, infection, and other wound complications exhibited large increases between 10 and 20 days postoperatively, while complication rates for new chronic pain, delirium, and dysrhythmia increased more gradually over the 30-day period studied. When specific surgical procedures were considered, 30-day complication rates ranged from 8.6% in single-level anterior cervical fusions to 27.3% in multilevel combined anterior and posterior lumbar spine fusions.This study demonstrates the usefulness of a longitudinal administrative database in assessing postoperative complication rates after spine surgery. Use of this database gave results that were comparable to those in prospective studies and superior to those obtained with nonlongitudinal administrative databases. Longitudinal administrative data may improve the understanding of overall and procedure-specific complication rates after spine surgery.

Abstract

To review the pathophysiology and therapeutic modalities availble for Nelson syndrome.We reviewed the current literature including managment for Nelson syndrome.For patients with NS, surgical intervention is often the first-line therapy. With refractory NS or tumors with extrasellar involvement, radiosurgery offers an important alternative or adjuvant option. Pharmacologic interventions have demonstrated limited usefulness, although recent evidence supports the feasibility of a novel somatostatin analog for patients with NS. Modern neuroimaging, improved surgical techniques, and the advent of stereotactic radiotherapy have transformed the management of NS.An up-to-date understanding of the pathophysiology underlying Nelson Syndrome and evidence-based management is imperative. Early detection may allow for more successful therapy in patients with Nelson Syndrome. Improved radiotherapeutic interventions and rapidly evolving pharmacologic therapies offer an opportunity to create targeted, multifocal treatment regiments for patients with Nelson Syndrome.

Abstract

The aim of this study was describe national trends in prevalence, demographics, hospital length of stay (LOS), hospital charges, and mortality for burn patients with and without inhalational injury and to compare to the National Burn Repository. Burns and inhalation injury cause considerable mortality and morbidity in the United States. There remains insufficient reporting of the demographics and outcomes surrounding such injuries. The National Inpatient Sample database, the nation's largest all-payer inpatient care data repository, was utilized to select 506,628 admissions for burns from 1988 to 2008 based on ICD-9-CM recording. The data were stratified based on the extent of injury (%TBSA) and presence or absence of inhalational injury. Inhalation injury was observed in only 2.2% of burns with <20% TBSA but 14% of burns with 80 to 99% TBSA. Burn patients with inhalation injury were more likely to expire in-hospital compared to those without (odds ratio, 3.6; 95% confidence interval, 2.7-5.0; P < .001). Other factors associated with higher mortality were African-American race, female sex, and urban practice setting. Patients treated at rural facilities and patients with hyperglycemia had lower mortality rates. Each increase in percent of TBSA of burns increased LOS by 2.5%. Patients with burns covering 50 to 59% of TBSA had the longest hospital stay at a median of 24 days (range, 17-55). The median in-hospital charge for a burn patient with inhalation injury was US$32,070, compared to US$17,600 for those without. Overall, patients who expired from burn injury accrued higher in-hospital charges (median, US$50,690 vs US$17,510). Geographically, California and New Jersey were the states with the highest charges, whereas Vermont and Maryland were states with the lowest charges. The study analysis provides a broad sampling of nationwide demographics, LOS, and in-hospital charges for patients with burns and inhalation injury.

Abstract

Intracranial fat migration following autologous fat graft and placement of a lumbar drain for cerebrospinal fluid leak after pineal cyst resection surgery has not been previously reported.The authors present a case of a 39-year-old male with a history of headaches who presented for removal of a pineal cyst from the pineal region. He subsequently experienced cerebrospinal fluid leak and postoperative Escherichia coli (E. Coli) wound infection, and meningitis, which were treated initially with wound washout and antibiotics in addition to bone removal and primary repair with primary suture-closure of the durotomy. A lumbar drain was left in place. The cerebrospinal fluid leak returned two weeks following removal of the lumbar drain; therefore, autologous fat graft repair and lumbar drain placement were performed. Three days later, the patient began experiencing right homonymous hemianopia and was found via computed tomography and magnetic resonance imaging to have autologous fat in the infra‑ and supratentorial space, including intraparenchymal and subarachnoid spread. Symptoms began to resolve with supportive care over 48 hours and had almost fully resolved within one week.This is the first known report of a patient with an autologous fat graft entering the subarachnoid space, intraparenchymal space, and ventricles following fat graft and lumbar drainage.This case highlights the importance of monitoring for complications of lumbar drain placement.

Abstract

Object Retrosigmoid (RS) and translabyrinthine (TL) surgery remain essential treatment approaches for symptomatic or enlarging acoustic neuromas (ANs). We compared nationwide complication rates and payments, independent of tumor characteristics, for these two strategies. Methods We identified 346 and 130 patients who underwent RS and TL approaches, respectively, for AN resection in the 2010-2012 MarketScan database, which characterizes primarily privately-insured patients from multiple institutions nationwide. Results Although we found no difference in 30-day general neurological or neurosurgical complication rates, in TL procedures there was a decreased risk for postoperative cranial nerve (CN) VII injury (20.2% vs 10.0%, CI 0.23-0.82), dysphagia (10.4% vs 3.1%, CI 0.10-0.78), and dysrhythmia (8.4% vs 2.3%, CI 0.08-0.86). Overall, there was no difference in surgical repair rates of CSF leak; however, intraoperative fat grafting was significantly higher in TL approaches (19.8% vs 60.2%, CI 3.95-9.43). In patients receiving grafts, there was a trend towards a higher repair rate after RS approach, while in those without grafts, there was a trend towards a higher repair rate after TL approach. Median total payments were $16,856 higher after RS approaches ($67,774 vs $50,918, p < 0.0001), without differences in physician or 90-day postoperative payments. Conclusions Using a nationwide longitudinal database, we observed that the TL, compared to RS, approach for AN resection experienced lower risks of CN VII injury, dysphagia, and dysrhythmia. There was no significant difference in CSF leak repair rates. The payments for RS procedures exceed payments for TL procedures by approximately $17,000. Data from additional years and non-private sources will further clarify these trends.

Abstract

The use of recombinant human bone morphogenetic protein (BMP) in the thoracolumbar spine remains controversial, with many questioning the risks and benefits of this new biologic.To describe national trends, incidence of complications, and revision rates associated with BMP use in thoracolumbar spine procedures.Administrative database study.A matched cohort of 52,259 patients undergoing thoracolumbar fusion surgery from 2006 to 2010 were identified in the MarketScan database. Patients without BMP treatment were matched 2:1 to patients receiving intraoperative BMP.Revision rates and postoperative complications.The MarketScan database was used to select patients undergoing thoracolumbar fusion procedures, with and without intraoperative BMP. We ascertained outcome measures using either International Classification of Disease, ninth revision, or Current Procedural Terminology coding, and matched groups were evaluated using a bivariate and multivariate analyses. Kaplan-Meier estimates of fusions failure rates were also calculated.Patients receiving intraoperative BMP underwent fewer refusions, decompressions, posterior and anterior revisions, or any revision procedure (single level 4.53% vs. 5.85%, p

Abstract

Study Design. Retrospective propensity score-matched analysis on a national database (MarketScan) between 2006 and 2010.Objective. To compare rates of neurological deficits after elective single level spinal procedures with and without intraoperative neuromonitoring, as well as associated payment differences and geographic variance.Summary of Background Data. Intraoperative neurophysiologic monitoring is a technique that may contribute to avoiding permanent neurological injury during some spine surgery procedures. However, it is unclear if all patients undergoing spine surgery benefit from neuromonitoring.Methods. An identified 85,640 patients underwent single level spinal procedures including anterior cervical discectomy and fusion (ACDF), lumbar fusion, lumbar laminectomy, or lumbar discectomy. Neuromonitoring was identified with appropriate Current Procedural Terminology (CPT) codes. Cohorts were balanced on baseline comorbidities and procedure characteristics using propensity score matching. Trauma and spinal tumors cases were excluded.Results. 12.66% patients received neuromonitoring intraoperatively. Lumbar laminectomies had reduced 30-day neurological complication rate with neuromonitoring (0.0% vs 1.18%, p = 0.002). Neuromonitoring did not correlate with reduced intraoperative neurological complications in ACDFs (0.09% vs 0.13%), lumbar fusions (0.32% vs 0.58%), or lumbar discectomy (1.24% vs. 0.91%). With the addition of neuromonitoring, payments for ACDFs increased 16.24% ($3,842), lumbar fusions 7.84% ($3,540), lumbar laminectomies 24.33% ($3,704), and lumbar discectomies 22.54% ($2.859). Significant geographic variation was evident. Some states had no recorded single-level spinal cases with concurrent neuromonitoring. Rates for ACDFs and lumbar fusions, laminectomies, and discectomies ranged as high as 61%, 58%, 22%, and 21%, respectively.Conclusions. With intraoperative neurological monitoring in single level procedures, neurological complications were only decreased among lumbar laminectomies. No difference was observed in ACDFs, lumbar fusions, or lumbar discectomies. There was a significant increase in total payments associated with the index procedure and hospitalization. We demonstrate significant geographic variation in neuromonitoring.

Abstract

Usage of recombinant human bone morphogenetic protein (rhBMP) in anterior cervical discectomy and fusion (ACDF) procedures is controversial. Studies suggest increased rates of dysphagia, hematoma or seroma, and severe airway compromise in anterior cervical spine procedures using rhBMP. The purpose of the present study was to determine and describe national utilization trends and complication rates associated with rhBMP usage in anterior cervical spine procedures.The MarketScan database from 2006 to 2010 was retrospectively queried to identify 91,543 patients who underwent ACDF with or without cervical corpectomy. Patient selection and outcomes were ascertained with use of ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) and CPT (Current Procedural Terminology) coding. A total of 3197 patients were treated with rhBMP intraoperatively. Mean follow-up was 588 days (interquartile range [IQR], 205 to 886 days) in the non-treated cohort and 591 days (IQR, 203 to 925 days) in the rhBMP-treated cohort. Multivariate logistic regression as well as propensity score analysis were used to evaluate the association of rhBMP usage with postoperative complications.In propensity score-adjusted models, rhBMP usage was associated with an increased risk of any complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.2 to 1.5) and specific complications such as hematoma or seroma (OR = 1.8, 95% CI = 1.4 to 2.3), dysphagia (OR = 1.3, 95% CI = 1.1 to 1.5), and any pulmonary complication (OR = 1.5, 95% CI = 1.2 to 1.8) within thirty days postoperatively. There were no significant differences in the rates of readmission, in-hospital mortality, referral to pain management, new malignancy, or reoperation between the two cohorts. Usage of rhBMP was associated with a mean increase of $5545 (19%) in total payments to the hospital and primary physician (p < 0.001).We found an increased overall rate of postoperative complications in patients receiving rhBMP for cervical spinal fusion procedures compared with patients not receiving rhBMP. Hematoma or seroma, pulmonary complications, and dysphagia were also more common in the rhBMP cohort. Usage of rhBMP in a case was associated with $311 greater payments to the surgeon and $4213 greater payments to the hospital.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Abstract

Usage of recombinant human bone morphogenetic protein (rhBMP) in anterior cervical discectomy and fusion (ACDF) procedures is controversial. Studies suggest increased rates of dysphagia, hematoma or seroma, and severe airway compromise in anterior cervical spine procedures using rhBMP. The purpose of the present study was to determine and describe national utilization trends and complication rates associated with rhBMP usage in anterior cervical spine procedures.The MarketScan database from 2006 to 2010 was retrospectively queried to identify 91,543 patients who underwent ACDF with or without cervical corpectomy. Patient selection and outcomes were ascertained with use of ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) and CPT (Current Procedural Terminology) coding. A total of 3197 patients were treated with rhBMP intraoperatively. Mean follow-up was 588 days (interquartile range [IQR], 205 to 886 days) in the non-treated cohort and 591 days (IQR, 203 to 925 days) in the rhBMP-treated cohort. Multivariate logistic regression as well as propensity score analysis were used to evaluate the association of rhBMP usage with postoperative complications.In propensity score-adjusted models, rhBMP usage was associated with an increased risk of any complication (odds ratio [OR] = 1.34, 95% confidence interval [CI] = 1.2 to 1.5) and specific complications such as hematoma or seroma (OR = 1.8, 95% CI = 1.4 to 2.3), dysphagia (OR = 1.3, 95% CI = 1.1 to 1.5), and any pulmonary complication (OR = 1.5, 95% CI = 1.2 to 1.8) within thirty days postoperatively. There were no significant differences in the rates of readmission, in-hospital mortality, referral to pain management, new malignancy, or reoperation between the two cohorts. Usage of rhBMP was associated with a mean increase of $5545 (19%) in total payments to the hospital and primary physician (p < 0.001).We found an increased overall rate of postoperative complications in patients receiving rhBMP for cervical spinal fusion procedures compared with patients not receiving rhBMP. Hematoma or seroma, pulmonary complications, and dysphagia were also more common in the rhBMP cohort. Usage of rhBMP in a case was associated with $311 greater payments to the surgeon and $4213 greater payments to the hospital.Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Abstract

The natural history of cervical degenerative disease with operative management has not been well described. Even with symptomatic and radiographic evidence of multilevel cervical disease, it is unclear whether single- or multilevel anterior cervical discectomy and fusion (ACDF) procedures produce superior long-term outcomes.To describe national trends in revision rates, complications, and readmission for patients undergoing single and multilevel ACDF.Administrative database study.Between 2006 and 2010, 92,867 patients were recorded for ACDF procedures in the Thomson Reuters MarketScan database. Restricting to patients with >24 months follow-up, 28,777 patients fulfilled our inclusion criteria, of which 12,744 (44%) underwent single-level and 16,033 (56%) underwent multilevel ACDFs.Revision rates and postoperative complications.We used the MarketScan database from 2006 to 2010 to select ACDF procedures based on Current Procedural Terminology coding at inpatient visit. Outcome measures were ascertained using either International Classification of Disease version 9 or Current Procedural Terminology coding.Perioperative complications were more common in multilevel procedures (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6; p

Abstract

Subarachnoid hemorrhage (SAH) causes significant morbidity and mortality. Pulmonary complications may be particularly frequent, but national data is lacking on the outcomes associated with acute respiratory distress syndrome (ARDS) in SAH patients. The aim of this study is to determine national trends for SAH patients with ARDS.The Nationwide Inpatient Sample Database (NIS) was utilized to sample 193,209 admissions for SAH with and without ARDS from 1993 to 2008 using ICD-9-CM coding. A multivariate stepwise regression analysis was performed.The incidence of ARDS in SAH has increased from 35.51% in 1993 to 37.60% in 2008. However, the overall mortality in SAH patients and in SAH patients with ARDS has decreased in the same period, from 42.30% to 31.99% and from 75.13% to 60.76% respectively. Multivariate analysis showed that the predictors of developing ARDS in SAH patients include older age, larger hospital size, and comorbidities such as epilepsy, cardiac arrest, sepsis, congestive heart failure, hypertension, chronic obstructive pulmonary disease, and hematologic, renal, or neurological dysfunction. Predictors of mortality in SAH patients include age and hospital complications such as coronary artery disease, ARDS, cancer, and hematologic, or renal dysfunction.SAH patients are at increased risk of developing ARDS and the identification of certain risk factors may alert and aid the practitioner in preventing worsening disease.

Abstract

The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.

Abstract

BACKGROUND: Spondyloepiphyseal dysplasia (SED) is a rare disease that causes vertebral abnormalities and short-trunk dwarfism. The two forms of SED are congenita and tarda. Each form arises in a genetically distinct fashion and manifests with a different set of complications. SED congenita is more severe, and patients usually display atlantoaxial instability and odontoid hypoplasia. Patients often have various neurologic deficits caused by compression of the spinal cord. The region most affected is the craniovertebral junction (CVJ). METHODS: A review of the PubMed Database, 1970 to the present, was performed using the search term "spondyloepiphyseal dysplasia" and limited to English-language articles. The search identified 22 articles discussing COL2A1 gene mutations and 10 clinical articles describing patients with SED and associated spinal abnormalities. RESULTS: Findings from the literature concerning diagnosis, presenting symptoms, and intervention taken are discussed. Additionally, a patient with a diagnosis of SED congenita who presented with bilateral hand numbness is described. The patient underwent a suboccipital craniotomy; posterior decompression of the foramen magnum, the arch of C1, and the lamina of C2; and instrumented fusion of C1-3 to relieve his symptoms. CONCLUSIONS: In this article, the authors survey the current literature surrounding neurosurgical interventions and present an algorithm for treatment.

Abstract

Brain tuberculoma has previously accounted for up to a third of new intracranial lesions in areas endemic with tuberculosis, but is unexpected in the United States and other Western countries with improved disease control. Here we show the importance of considering this diagnosis in at-risk patients, even with no definitive pulmonary involvement. We describe a young man who presented with partial seizures and underwent craniotomy for resection of a frontoparietal tuberculoma. He subsequently completed six months of antituberculosis therapy and was doing well without neurological sequelae or evidence of recurrence five months after completion of therapy. With resurgence of tuberculosis cases in the United States and other Western countries, intracerebral tuberculoma should remain a diagnostic consideration in at-risk patients with new space occupying lesions. Mass lesions causing neurological sequelae can be safely addressed surgically and followed with antituberculosis therapy.

Abstract

Low-grade gliomas (LGG) constitute a class of slow-growing primary brain neoplasms. Patients with clinically and radiographically suspected LGG have two initial surgical options, biopsy or resection. Biopsy can provide a histological diagnosis with minimal risk but does not offer a direct treatment. Resection may have additional benefits such as increasing survival and delaying recurrence, but is associated with a higher risk for surgical morbidity. There remains controversy about the role of biopsy versus resection and the relative clinical outcomes for the management of LGG.To assess the clinical effectiveness of biopsy compared to surgical resection in patients with a new lesion suspected to be a LGG.The following electronic databases were searched: Cochrane Central Register of Controlled Trials (CENTRAL) (2012, Issue 11), MEDLINE (1950 to week 3 November 2012), EMBASE (1980 to Week 46 2012). Unpublished and grey literature including Metaregister, Physicians Data Query, www.controlled-trials.com/rct, www.clinicaltrials.gov, and www.cancer.gov/clinicaltrials were also queried for ongoing trials.Patients of any age with a suspected intracranial LGG receiving biopsy or resection within a randomized clinical trial (RCT) or controlled clinical trial (CCT) were included. Patients with prior resections, radiation therapy, or chemotherapy for LGG were excluded. Outcome measures included overall survival (OS), progression free survival (PFS), functionally independent survival (FIS), adverse events, symptom control, and quality of life (QoL).A total of 2764 citations were searched and critically analyzed for relevance. This effort was undertaken by three independent review authors.No RCTs of biopsy or resection for LGG were identified. Twenty other studies were retrieved for analysis based on pre-specified selection criteria. Ten studies were retrospective or literature reviews. Three studies were prospective but were limited to tumor recurrence or the extent of resection. One study was a population-based parallel cohort and not an RCT. Four studies were RCTs, however patients were randomized with respect to varying radiotherapy regimens to assess timing and dose of radiation. One RCT was focused on high-grade gliomas and not LGG. One last RCT evaluated diffusion tensor imaging (DTI)-based neuro-navigation for surgical resection.Currently there are no randomized clinical trials or controlled clinical trials available on which to base clinical decisions. Therefore, physicians must approach each case individually and weigh the risks and benefits of each intervention until further evidence is available. Future research could focus on randomized clinical trials to determine outcomes benefits for biopsy versus resection.

Abstract

Endonasal procedures may be necessary during management of craniofacial trauma. When a skull base fracture is present, these procedures carry a high risk of violating the cranial vault and causing brain injury or central nervous system infection.A 52-year-old bicyclist was hit by an automobile at high speed. He sustained extensive maxillofacial fractures, including frontal and sphenoid sinus fractures (Fig. 1). He presented to the emergency room with brisk nasopharyngeal hemorrhage, and was intubated for airway protection. He underwent emergent stabilization of his nasal epistaxis by placement of a Foley catheter in his left nare and tamponade with the Foley balloon. A six-vessel angiogram showed no evidence of arterial dissection or laceration. Imaging revealed inadvertent insertion of the Foley catheter and deployment of the balloon in the frontal lobe (Fig. 2). The balloon was subsequently deflated and the Foley catheter removed. The patient underwent bifrontal craniotomy for dural repair of CSF leak. He also had placement of a ventriculoperitoneal shunt for development of post-traumatic hydrocephalus. Although the hospital course was a prolonged one, he did make a good neurological recovery.The authors review the literature involving violation of the intracranial compartment with medical devices in the settings of craniofacial trauma.Caution should be exercised while performing any endonasal procedure in the settings of trauma where disruption of the anterior cranial base is possible.

Abstract

Spontaneous intracranial hypotension (SIH) is an uncommon syndrome widely attributed to CSF hypovolemia, typically secondary to spontaneous CSF leak. Although commonly associated with postural headache and variable neurological symptoms, one of the most severe consequences of SIH is bilateral subdural hematomas with resultant neurological deterioration.We present the case of a patient diagnosed with SIH secondary to an anteriorly positioned thoracic osteophyte with resultant dural disruption, who after multiple attempts at nonsurgical management developed bilateral subdural hematomas necessitating emergent surgical intervention. The patient underwent a unilateral posterior repair of his osteophyte with successful anterior decompression. At 36months follow up, the patient reported completely resolved headaches with no focal neurological deficits.We outline our posterior approach to repair of the dural defect and review the management algorithm for the treatment of patients with SIH. We also examine the current hypotheses as to the origin, pathophysiology, diagnosis and treatment of this syndrome.A posterior approach was utilized to repair the dural defect caused by an anterior thoracic osteophyte in a patient with severe SIH complicated by bilateral subdural hematomas. This approach minimizes morbidity compared to an anterior approach and allowed for removal of the osteophyte and repair of the dural defect.

Abstract

Spinal cord intramedullary metastases are uncommon and treatment options are limited. We reviewed our experience treating these lesions with radiosurgery to assess safety and efficacy, and to define preliminary treatment recommendations. With Institutional Review Board approval, we identified nine patients with 11 metastases treated with radiosurgery at Stanford University Hospital, between 2000 and 2010. We also reviewed all available published series discussing the treatment of spinal cord metastases. Our patients ranged in age from 33 years to 77 years (median 63 years) and included seven women and two men. Tumors ranged in size from 0.12 cm(3) to 6.4 cm(3) (median 0.48 cm(3)). Five were from breast cancer, two were non-small cell lung cancers, one was a cystic adenocarcinoma, and one was from an epithelioid hemangioepithelioma. All patients had neurologic deficits and multiple other metastases. We delivered 14 Gy to 27 Gy (median 21 Gy) in one to five (median 3) fractions. Complete follow-up was available for all nine patients. One patient remains alive 14 months after therapy. Of the eight deceased patients, survival ranged from one month and two days to nine months and six days (median four months and four days). There were no local recurrences or worsened neurological deficits. To our knowledge this is the largest reported series of spinal cord intramedullary metastases treated with radiosurgery. Survival was poor due to systemic disease, but radiosurgery appears to be safe and prevented local recurrences. With fewer sessions than conventional radiation and less morbidity than surgery, we feel radiosurgery is appropriate for the palliative treatment of these lesions.

Abstract

Improved patient outcomes have been associated with high-caseload hospitals for a multitude of conditions. This study analyzed adult patients undergoing surgical resection or biopsy of primary brain tumors. The aim of this study is two-fold: (1) to evaluate whether the trend towards centralization of primary brain tumor care in the US has continued during the period of between 2001 and 2007, and (2) to analyze volume-outcome effects.Surgical volume trends of adults undergoing resection/biopsy of primary supratentorial brain tumors were analyzed using the Nationwide Inpatient Sample. High- and low-caseload hospitals were defined as those performing in the highest and lowest quintile of procedures, respectively. Length of stay (LOS), mortality and discharge disposition were the main outcomes of interest.NIS estimated 124,171 patients underwent resection/biopsy of primary supratentorial brain tumors between 2001 and 2007 in the US. The average number of annual resections in the highest 2 % and lowest 25 % caseload hospitals were 322 and 12 cases, respectively. Surgeries in high-caseload hospitals increased by 137 %, while those in low-caseload centers declined by 16.0 %. Overall, mortality decreased 35 %, with a reduction of 45 % in high- (from 2.2 % to 1.2 %) and 19 % in low- (from 3.2 % to 2.6 %) caseload hospitals. High-caseload centers had lower LOS than hospitals with lower caseload centers (6.4 vs. 8.0 days, p

Abstract

Chordomas are rare, malignant bone tumors of the axial skeleton, occurring particularly at the cranial base or in the sacro-coccygeal region. Although slow growing, chordomas are locally aggressive and challenging to treat. We evaluate the outcomes of skull base and spinal chordomas in 20 patients treated with CyberKnife (CK) stereotactic radiosurgery (SRS) (Accuray, Sunnyvale, CA, USA) between 1994 and 2010 at Stanford Hospital. There were 12 males and eight females (10-78 years; median age: 51.5 years). Eleven patients received CK as primary adjuvant therapy and nine patients received CK for multiple recurrences. The average tumor volume treated was 16.1cm(3) (2.4-45.9 cm(3)), with a mean marginal dose of 32.5 Gy (18-50 Gy). Median follow-up was 34 months (2-131 months). Overall, tumor control was achieved in 11 patients (55%), with eight patients showing tumor size reduction. However, nine patients showed progression and eventually succumbed to the disease (mean time from CK to death was 26.3 months). Of the patients treated with CK as the primary adjuvant therapy, 81.8% had stable or improved outcomes. Only 28.6% of those treated with CK for recurrences had stable or improved outcomes. The overall Kaplan-Meyer survival at five years from the first CK treatment was 52.5%. Moderate tumor control rates can be achieved with few complications with CK SRS. Poor control is associated with complex multiple surgical resections, long delay between initial resection and CK therapy, and recurrently aggressive disease uncontrolled by prior radiation.

Abstract

Dialysis-associated destructive spondyloarthropathy (DSA) is the major bony complication of end-stage renal disease, most commonly found in the lower cervical region. The risk factors for developing dialysis-associated DSA include duration of hemodialysis and patient age. Patients with DSA have a higher incidence of osteoporosis and poor bone mineral density, which may place them at greater risk of atraumatic fractures, instrumentation failure, and neurologic compromise.We describe a case of cervical radiculopathy due to dialysis-associated DSA atraumatic vertebral body fractures with a postoperative course that was complicated by instrumentation failure. We reviewed the literature regarding all 138 published cases, presenting the complications, surgical treatment options, and outcomes.A 44-year-old dialysis-dependent man presented with acute neck pain, radiculopathy, and weakness due to atraumatic fracture of C5 and C6 vertebral bodies. He underwent anterior C5 and C6 corpectomies, reconstruction with mesh cage and plate, and supplemental posterior instrumentation (C4-T1). Six weeks later, a computed tomography scan revealed anterior translation across the instrumented area with failure of the posterior instrumentation. He subsequently underwent traction, revision reinstrumentation from C2 to T5, and placement of external halo ring/jacket for 6 months. At 18 months later, he remains ambulatory without evidence of construct failure.Patients with renal osteodystrophy present a challenge for the spine surgeon due to compromised bone density. Hardware failure at the bone-construct interface is common in these patients, with revision surgery needed in 22% of published cases. Longer constructs with circumferential instrumentation and halo immobilization may minimize the risk of pseudoarthrosis and construct pull-out.

Abstract

Although vertebral and epidural metastases are common, intradural metastases and intramedullary spinal cord metastases are rare. The indications for the treatment of intramedullary spinal cord metastases remain controversial. We present the first biopsy-proven case of an intramedullary spinal cord metastasis from adenocarcinoma of the prostate.Our patient was a 68-year-old right-handed Caucasian man with a Gleason grade 4 + 3 prostate adenocarcinoma who had previously undergone a prostatectomy, androgen blockade and transurethral debulking. He presented with new-onset saddle anesthesia and fecal incontinence. Magnetic resonance imaging demonstrated a spindle-shaped intramedullary lesion of the conus medullaris. Our patient underwent decompression and an excisional biopsy; the lesion's pathology was consistent with metastatic adenocarcinoma of the prostate. Postoperatively, our patient received CyberKnife® radiosurgery to the resection cavity at a marginal dose of 27Gy to the 85% isodose line. At three months follow-up, our patient remains neurologically stable with no new deficits or lesions.We review the literature and discuss the indications for surgery and radiosurgery for intramedullary spinal cord metastases. We also report the novel use of stereotactic radiosurgery to sterilize the resection cavity following an excisional biopsy of the metastasis.

Abstract

Hemangiopericytoma is a rare and aggressive meningeal tumor. Although surgical resection is the standard treatment, hemangiopericytomas often recur with high incidences of metastasis. The purpose of this study was to evaluate the role of CyberKnife stereotactic radiosurgery (CK) in the management of recurrent, metastatic, and residual hemangiopericytomas.In a review of the Stanford radiosurgery database between 2002 and 2009, the authors found 14 patients who underwent CK therapy for recurrent, metastatic, and residual hemangiopericytomas. A total of 24 tumors were treated and the median patient age was 52 years (range 29-70 years) at the time of initial CK therapy. The median follow-up period was 37 months (10-73 months) and all patients had been previously treated with surgical resection. Mean tumor volume was 9.16 cm3 and the mean marginal and maximum radiosurgical doses to the tumors were 21.2 Gy and 26.8 Gy, respectively.Of the 24 tumors treated, 22 have clinical follow-up data at this time. Of those 22 tumors, 12 decreased in size (54.5%), 6 remained unchanged (27.3%), and 4 showed recurrence (18.2%) after CK therapy. Progression-free survival rate was 95%, 71.5%, and 71.5% at 1, 3, and 5 years after multiple CK treatments. The 5-year survival rate after CK was 81%.CK is an effective and safe management option for hemangiopericytomas. The current series demonstrates a tumor control of 81.8%. Other institutions have demonstrated similar outcomes with stereotactic radiosurgery, with tumor control ranging from 46.4% to 100%.

Abstract

Whether there is an increased surgical risk in elderly patients who undergo craniotomy for meningioma resection remains a point of controversy. Utilising multicentre, prospective data from the National Surgical Quality Improvement Program, the present study sought to address this controversy.All patients who underwent a craniotomy for resection of intracranial meningioma (current procedural terminology codes 61512 and 61519) between 1997 and 2006 at 123 VA hospitals around the country were included. After controlling for preoperative factors such as ASA class, race, diabetes mellitus, disseminated cancer, tobacco use, tumour location and functional health status in a multivariate logistic regression model, the effect of elderly age (age greater than 70 years) on 30 day mortality was determined.Our study included 1281 patients who underwent surgical resection of an intracranial meningioma. Although each VA completed a different number of operations, we are able to provide case volume data for approximately 60 of the 123 hospitals. The elderly cohort represented 21.2% (n=258) of our total study population. Elderly patients had a higher 30 day mortality (12.0%) than younger subjects (4.6%) (p<0.0001). Similarly, elderly patients were more likely to have one or more complications (29.8% vs 13.1%, p<0.0001). Multivariate logistic regression identified age, functional status, preoperative disseminated cancer and tumour location as important predictors of 30 day mortality. After controlling for preoperative comorbidities and risk factors, the odds of perioperative mortality in elderly patients were three times that of younger patients (OR 3.0, 95% CI 1.7 to 5.3, p=0.0102).After carefully controlling for various patient characteristics, ASA class and functional status, elderly patients have poorer outcome after surgical resection of intracranial meningioma than younger subjects.

The role of radiosurgery in the treatment of craniopharyngiomasNEUROSURGICAL FOCUSVeeravagu, A., Lee, M., Jiang, B., Chang, S. D.2010; 28 (4)

Abstract

The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.

Abstract

Syringomyelia is an abnormal cystic dilatation of the spinal cord caused by excessive accumulation of CSF. Patients can develop various neurologic deficits secondary to untreated syringomyelia, some of which can be permanent despite surgical intervention.The authors present a patient with syringomyelia, aortic coarctation, and tethered cord syndrome. Serial radiographic imaging demonstrated initial significant reduction of the thoracic syrinx after coarctation repair and release of tethered cord. However, subsequent follow-up imaging revealed partial recurrence.This case provides evidence of a possible cause-effect relationship between syringomyelia and tethered cord. It demonstrates the indication of surveillance imaging of the entire spine to ensure that all potential etiologies of syringomyelia are identified and treated. Furthermore, it illustrates the complex dynamic nature of syrinx physiology and reinforces the importance of serial follow-up studies after surgical intervention.

Abstract

Statins are thought to have tumorolytic properties, reducing angiogenesis by inhibiting pro-angiogenic factors and inducing apoptosis of mural pericytes within the tumor vascular tree.An orthotopic mouse glioblastoma (GL-26) model was used to investigate the effect of simvastatin on glioblastoma vasculature in vivo. GL-26 cells were implanted into the striatum of C5LKa mice treated with either control, low- or high-dose simvastatin. Brains were analyzed for necrotic volume, apoptosis, morphology and pericytic cells within the vascular tree.Low-dose simvastatin increased necrosis and apoptosis compared to both control and high-dose simvastatin groups. High-dose simvastatin increased vessel caliber by reducing pericytic cells along the tumor vessel wall compared to both control and low-dose simvastatin groups.Simvastatin has a dual effect on tumorigenesis. At high doses, it may worsen instead of 'normalizing' tumor angio-architecture, albeit low doses affect tumor cell survival by promoting necrosis and apoptosis.

Abstract

Glioblastoma multiforme (GBM) is a WHO grade IV malignant brain tumor with poor prognosis, despite advances in surgical and adjuvant therapy. GBM is characterized by areas of central necrosis and high levels of angiogenesis, during which increased vascular permeability allows for the extravasation of endothelial progenitor cells to support blood vessel and tumor growth. The purpose of this study was to characterize changes in tumor vascular permeability, vascular density and vessel morphology in vivo during angiogenesis.An orthotropic murine (GL26) glioblastoma model was used in this study. in vivo serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in combination with histologic and molecular genetic analyses was performed to correlate in vivo imaging of vascular development.DCE-MRI revealed a significant change in tumor vessel permeability dependent upon tumor progression and size. Time to max signal intensity displayed a stepwise increase between days 21 and 24 (p<0.05), a critical period before exponential tumor growth during which a significant increase in tumor vascular density and vessel caliber is observed on histology. Furthermore, quantitative real-time PCR revealed a corollary increase in angiogenic signaling molecules before the observed changes on DCE-MRI.In vivo changes of orthotopic glioma blood vessel permeability as shown by DCE-MRI correlates with histologic quantification of vascular density and vessel caliber as well as with the molecular expression of angiogenic factors. DCE-MRI is a useful tool for non-invasive in vivo monitoring of angiogenesis in pre-clinical tumor models.

Abstract

The cancer stem cell (CSC) theory hypothesizes that a small subpopulation of cells within a tumor mass is responsible for the initiation and maintenance of the tumor. The idea that brain tumors arise from this specific subset of self-renewing, multipotent cells that serve as the locus for tumor formation, has gained great support as evidenced by recent advancements in the biology of breast and colon cancer. It is well established that recruitment of bone marrow-derived proangiogenic progenitor cells and angiogenesis are key events in the process of brain tumor formation; however, the orchestration of these events by the CSC population has only recently been unveiled. In this review, we first introduce the CSC theory and examine the functional development of the vascular niche, its purpose, constituents, and contribution to the development of the CSC-vascular niche complex. Through this discussion, we aim to shed light on the events that may be targeted for therapeutic intervention.

Abstract

To systematically analyze patient outcomes after repeat transsphenoidal (TS) surgery for recurrent Cushing's disease.We retrospectively reviewed records of all patients with recurrent Cushing's disease who underwent repeat TS surgery for resection of a pituitary corticotroph adenoma at the University of Virginia Medical Center from 1992 to 2006. Remission at follow-up was defined as a normal postoperative 24-hour urine free cortisol, or continued need for glucocorticoid replacement after repeat TS surgery. Recurrence of the disease was defined as an elevated 24-hour urine free cortisol with clinical symptoms consistent with Cushing's disease while not receiving glucocorticoid replacement. Multivariate logistic regression was performed to evaluate the effect of potential predictors on remission. Recurrence rates, subsequent treatments, and the final endocrine status of the patients are presented.We identified 36 patients who underwent repeat TS surgery for recurrent Cushing's disease. The mean age of the patients was 40.3 years (range, 17.1-63.0 yr), and 26 were women. The median time to recurrence after initial successful TS surgery was 36 months (range, 4 mo-16 yr). Remission after repeat TS surgery was observed in 22 (61%) of the 36 patients. During the same time period, of the 338 patients who underwent first-time TS surgery for Cushing's disease, remission was achieved in 289 (85.5%). The odds of failure (to achieve remission) for patients with repeat TS surgery for recurrent Cushing's disease were 3.7 times that of patients undergoing first-time TS surgery (odds ratio, 3.7; 95% confidence interval, 1.8-7.8). Two of the 22 patients with successful repeat TS surgery had a second recurrence at 6 and 11 months, respectively. Complete biochemical and clinical remission after stereotactic radiosurgery, adrenalectomy, and ongoing ketoconazole therapy was achieved in 30 (83.3%) of the 36 patients, and active disease continued in 6 patients (16.7%).Although the success of repeat TS surgery for recurrence of Cushing's disease is less than that of initial surgery, a second procedure offers a reasonable possibility of immediate remission. If the operation is not successful, other treatments, including pituitary radiation, medical therapy, and even bilateral adrenalectomy, are required.

Abstract

Neurosurgical interventions for moyamoya disease (MMD) in pediatric patients include direct, indirect, and combined revascularization procedures. Each technique has shown efficacy in the treatment of pediatric MMD; however, no single study has demonstrated the superiority of one technique over another. In this review, the authors explore the various studies focused on the use of these techniques for MMD in the pediatric population. They summarize the results of each study to clearly depict the clinical outcomes achieved at each institution that had utilized direct, indirect, or combined techniques. In certain studies, multiple techniques were used, and the clinical or radiological outcomes were compared accordingly. Direct techniques have been shown to aid a reduction in perioperative strokes and provide immediate revascularization to ischemic areas; however, these procedures are technically challenging, and not all pediatric patients are appropriate candidates. Indirect techniques have also shown efficacy in the pediatric population but may require a longer period for revascularization to occur and perfusion deficits to be reversed. The authors concluded that the clinical efficacy of one technique over another is still unclear, as most studies have had small populations and the same outcome measures have not been applied. Authors who compared direct and indirect techniques noted approximately equal clinical outcomes with differences in radiological findings. Additional, larger studies are needed to determine the advantages and disadvantages of the different techniques for the pediatric age group.

Abstract

Glutaric acidemia type I (GA-I) is a rare, autosomal recessive metabolic disorder that leads to severe dystonia, basal ganglia degeneration, and bilaterally enlarged anterior middle cranial fossae. The current management of this disease includes early diagnosis with newborn screening, prevention of catabolism, carnitine supplementation, and a strict dietary protein restriction. Neurosurgical evaluation and intervention may be necessary in patients with structural lesions associated with this disease. In this report, the authors present two pediatric patients with GA-I and discuss the neurosurgical aspects of this rare medical disorder.

Abstract

Direct contact between cellular and extracellular matrix (ECM) proteins is necessary for a diverse array of physiologic processes including cellular activation, migration, proliferation, and differentiation. These direct interactions are modulated by cell adhesion molecules (CAMs) such as integrins, selectins, cadherins, and immunoglobulins. Integrin signaling also plays a key role in tumor growth, angiogenesis, and metastasis. Recent advances in the discovery and characterization of CAMs and their receptors, most notably integrin alpha(v)beta(3), and the clarification of their roles in disease states have laid the groundwork for the development and clinical implementation of novel anti-cancer treatments. Integrin alpha (v)beta(3) is a glycoprotein membrane receptor which recognizes ECM proteins expressing an arginine-glycine-aspartic acid (RGD) peptide sequence. The receptor is highly expressed on activated tumor endothelial cells, but not resting endothelial cells and normal organ systems, thus making alpha(v)beta(3) an appropriate target for anti-angiogenic therapeutics. In addition, alpha(v)beta(3) is also expressed on tumor cells, allowing for both tumor cell and tumor vasculature targeting of anti-integrin therapy. Throughout the past decade, numerous patents have been published and issued using alpha(v)beta(3) antagonists for the prevention and/or treatment of cancer, with many antagonists demonstrating positive pre-clinical anti-angiogenic and anti-tumor results. This review will focus on the key points and distinguishing factors for patents which use antibodies, RGD peptides, non-RGD peptides, peptidomimetics, and amine salts as alpha(v)beta(3) antagonists.

Abstract

Vascular endothelial growth factor A (VEGF-A) and its receptors, Flt-1/FLT-1 (VEGFR-1) and Flk-1/KDR (VEGFR-2), are key regulators of tumor angiogenesis and tumor growth. The purpose of this study was to determine the antiangiogenic and antitumor efficacies of a vasculature-targeting fusion toxin (VEGF(121)/rGel) composed of the VEGF-A isoform VEGF(121) linked with a G(4)S tether to recombinant plant toxin gelonin (rGel) in an orthotopic glioblastoma mouse model by use of noninvasive in vivo bioluminescence imaging (BLI), MRI, and PET.Tumor-bearing mice were randomized into 2 groups and balanced according to BLI and MRI signals. PET with (64)Cu-1,4,7,10-tetraazacyclododedane-N,N',N'',N'''-tetraacetic acid (DOTA)-VEGF(121)/rGel was performed before VEGF(121)/rGel treatment. (18)F-Fluorothymidine ((18)F-FLT) scans were obtained before and after treatment to evaluate VEGF(121)/rGel therapeutic efficacy. In vivo results were confirmed with ex vivo histologic and immunohistochemical analyses.Logarithmic transformation of peak BLI tumor signal intensity revealed a strong correlation with MRI tumor volume (r = 0.89, n = 14). PET with (64)Cu-DOTA-VEGF(121)/rGel before treatment revealed a tumor accumulation (mean +/- SD) of 11.8 +/- 2.3 percentage injected dose per gram at 18 h after injection, and the receptor specificity of the tumor accumulation was confirmed by successful blocking of the uptake in the presence of an excess amount of VEGF(121). PET with (18)F-FLT revealed significant a decrease in tumor proliferation in VEGF(121)/rGel-treated mice compared with control mice. Histologic analysis revealed specific tumor neovasculature damage after treatment with 4 doses of VEGF(121)/rGel; this damage was accompanied by a significant decrease in peak BLI tumor signal intensity.The results of this study suggest that future clinical multimodality imaging and therapy with VEGF(121)/rGel may provide an effective means to prospectively identify patients who will benefit from VEGF(121)/rGel therapy and then stratify, personalize, and monitor treatment to obtain optimal survival outcomes.

Abstract

Patients with atypical trigeminal neuralgia (TN) have unilateral pain in the trigeminal distribution that is dull, aching, or burning in nature and is constant or nearly constant. Studies of most radiosurgical and surgical series have shown lower response rates in patients with atypical TN. This study represents the first report of the treatment of atypical TN with frameless CyberKnife stereotactic radiosurgery (SRS).Between 2002 and 2007, 7 patients that satisfied the criteria for atypical TN and underwent SRS were included in our study. A 6-8-mm segment of the trigeminal nerve was targeted, excluding the proximal 3 mm at the brainstem. All patients were treated in a single session with a median maximum dose of 78 Gy and a median marginal dose of 64 Gy.Outcomes in 7 patients with a mean age of 61.6 years and a median follow-up of 20 months are reported. Following SRS, 4 patients had complete pain relief, 2 had minimal pain relief with some decrease in the intensity of their pain, and 1 patient experienced no pain relief. Pain relief was reported within 1 week of SRS in 4 patients and at 4 months in 2 patients. After a median follow-up of 28 months, pain did not recur in any of the 4 patients who had reported complete pain relief. Complications after SRS included bothersome numbness in 3 patients and significant dysesthesias in 1 patient.The authors have previously reported a 90% rate of excellent pain relief in patients with classic TN treated with CyberKnife SRS. Compared with patients with classic TN, patients with atypical TN have a lower rate of pain relief. Nevertheless, the nearly 60% rate of success after SRS achieved in this study is still comparable to or better than results achieved with any other treatment modality for atypical TN.

Abstract

Gout in the axial spine is rare. We present a case report on a renal transplant patient who developed fever and acute back pain at the L5 through S1 level secondary to sodium urate deposits. We review the literature on this rare disease and propose a management algorithm based on a resulting analysis.A 37-year-old man with a history of gout and a renal transplant for IgA nephropathy presented with acute back pain and fever without evidence of neurological deficits. Magnetic resonance imaging revealed a uniformly contrast-enhancing infiltrative process involving the right pedicle, lamina, and inferior facet of the L5 vertebra. Computed tomography-guided needle biopsy revealed a friable white tissue consistent with sodium urate crystals. Conservative treatment with steroids and narcotics was used with good symptomatic relief.Although few cases of gout involving the spine have been reported, its prevalence is likely grossly underestimated. Most patients have a history of gout and have elevated levels of serum urate level on presentation. The disease most commonly involves the lumbar spine. Patients usually have neurological deficits on presentation, and surgical decompression produces favorable outcomes. However, conservative medical management is appropriate for those with back pain only. Aggressive control of hyperuricemia is essential regardless of the method of treatment.

Abstract

New blood vessel formation (angiogenesis) is fundamental to the process of tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) family of ligands and receptors are well established as key regulators of these processes. VEGF is a glycoprotein with mitogenic activity on vascular endothelial cells. Specifically, VEGF-receptor pathway activation results in signaling cascades that promote endothelial cell growth, migration, differentiation, and survival from pre-existing vasculature. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Recent identification of seven VEGF ligand variants (VEGF [A-F], PIGF) and three VEGF tyrosine kinase receptors (VEGFR- [1-3]) has led to the development of several novel inhibitory compounds. Clinical trials have shown inhibitors to this pathway (anti-VEGF therapies) are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. Having been first described in the 1980s, VEGF patenting activity since then has focused on anti-cancer therapeutics designed to inhibit tumoral vascular formation. This review will focus on patents which target VEGF-[A-F] and/or VEGFR-[1-3] for use in anti-cancer treatment.

Abstract

The brain is a privileged site of systemic cancer metastasis. The stages of the metastatic journey from the periphery to the brain are driven by molecular events that tie the original site of disease to the distant host tissue. This preference is not arbitrary but rather a directed phenomenon that includes such critical steps as angiogenesis and the preparation of the premetastatic niche. It appears that the connection between naive brain and cancer cells is made in advance of any metastatic breach of the blood-brain barrier. This contributes to the preferential homing of cancer cells to the brain. Delineation of the guidance mechanisms and elements that influence cancer cell motility and dormancy are important for the advancement of treatment modalities aimed at the remediation of this devastating disease.

Abstract

Glioblastoma multiforme (GBM) is one of the most aggressive primary brain tumors, with a grim prognosis despite maximal treatment. Advancements in the past decades have not significantly increased the overall survival of patients with this disease. The recurrence of GBM is inevitable, its management often unclear and case dependent. In this report, the authors summarize the current literature regarding the natural history, surveillance algorithms, and treatment options of recurrent GBM. Furthermore, they provide brief discussions regarding current novel efforts in basic and clinical research. They conclude that although recurrent GBM remains a fatal disease, the literature suggests that a subset of patients may benefit from maximal treatment efforts. Nevertheless, further research effort in all aspects of GBM diagnosis and treatment remains essential to improve the overall prognosis of this disease.